Sample loading apparatus



Jan. 6, 1970 A. R. THOMSON ET AL 3,487,678

SAMPLE LOADING APPARATUS Filed Dec. 16. 1966 United States Patent3,487,678 SAMPLE LOADING APPARATUS Alan Russell Thomson, Abingdon, andJohn William Eveleigh, Wantage, England, assignors to United KingdomAtomic Energy Authority, London, England Filed Dec. 16, 1966, Ser. No.602,267 Claims priority, application Great Britain, Mar. 25, 1966,13,440/ 66 Int. 'Cl. G01n 1/00 US. Cl. 73--61.1 20 Claims ABSTRACT OFTHE DISCLOSURE Apparatus for automatically loading samples for analysison to a chromatography column has a transfer member that is stepwisemoved along a path. A plurality of sample locating chambers are locatedin a spaced relationship on the transfer member and extend through themember. A fluid inlet duct and a fluid outlet duct are located relativeto the transfer member so that as each chamber is, in turn, registeredwith the ducts, the ducts are connected with each successive chamber.The ducts are connected by sealing to opposite sides of a fluidpassageway through a given chamber, such that fluid can flow from theinlet duct through the given chamber and out the outlet duct leading toa column.

This invention relates to analysing equipment and is particularly, butnot exclusively, concerned with equipment suitable for use in columnchromatography.

Determination of protein and polynucleotide structures require largenumbers of quantitative analyses of mixtures of amino acids andnucleotides. Recent advances in column chromatography have significantlyreduced the time required for one analysis e.g. for amino acids from 24to 2 hrs. and since suitable automatic systems are now available it isdesirable that means he provided whereby a predetermined number ofsamples for analysis may be automatically loaded, in turn, and atpreselected times onto a column.

According to the invention means for automatically loading samples foranalysis on to a chromatography column comprises a transfer member, aplurality of sample locating chambers located in a spaced relationshipon said transfer member, a fluid inlet duct and a fluid outlet ductconnectable with said chamber, said fluid outlet duct leading to saidcolumn and means for stepwise moving the transfer member such that eachchamber is, in turn, simultaneously registerable with said inlet andoutlet ducts.

Preferably fluid sealing means are provided to seal the sample chamberto the ducts.

According to a further aspect of the invention, means for automaticallyloading samples for analysis onto a chromatography column comprises atransfer member, a plurality of apertures in a spaced relationship insaid member, means for locating a sample in each aperture, means forstepwise moving the member such that each aperture is held in exclusiveregister with fluid inlet and outlet ducts and fluid sealing meansbetween the member and each of the said ducts.

The sealing means may incorporate a cam associated and operable with thetransfer member moving means such a sealing pressure applied by said camis operable when one of the sample holding apertures is in register withthe said ducts.

In a preferred form of the invention, the transfer member comprises ablock having a plurality of apertures arranged in a spaced linearrelationship and the samples are located in containers positionable ineach aperture.

To enable the nature of the invention to be more readily understood, anembodiment of the invention will now be described, solely by way ofexample with reference to the accompanying drawing. In the drawing FIG.1 is a sectional elevation of a sampling loading device.

FIG. 2 is a sectional end elevation on the line 11 of FIG. 1.

Referring to the drawing the sample loading device comprises arectangular block incorporating a plurality of sample containers 2, theblock being arranged to slide longitudinally on guide rails 3 wherebyeach sample container may be moved in a pre-determined sequence toregister with inlet and outlet ducts 4 and 5, the inlet duct connectingwith an eluent pump (not shown) and the outlet duct leading to ananalytical column (not shown).

The block 1 is provided with a plurality of equally spaced verticalapertures 6, said apertures being dimensioned to easily receive thesample containers 2. Each aperture is shaped to support the flangedupper end of a sample container. The containers are tubular, having aninternal shoulder 7 at the lower end arranged to support a porous disc8. A resilient O-ring located in an annular groove on the outer surfaceof the container acts as a seal between the block and the container. Theinterior of the container is partly filled with a sample supportmaterial 9, for example, a resin or other absorbent bed material.

With some sample materials it is desirable to exclude the atmospherewhile awaiting analysis and a cover 33 is provided, for this purpose,above the movable block. The cover is resiliently secured to a pair ofside plates 12 such that the block may freely move under the cover.

The block 1 is basically rectangular inshape having a bottom flange orextension 10 at each lower longitudinal edge. Each upper longitudinaledge is provided with a series of vertical grooves 11 which extend intothe block to form a rack. The grooves 11 are spaced mid-Way between thecontainer locating apertures 6.

Each block flange 10 rests on a guide rail 3 and each guide isresiliently secured to a side plate 12 by two screws 13 and soft rubbermembers 14. The side plates are spaced apart on a base plate 15 whichalso forms a locating base for a conventional electric drive motor (notshown).

A drive shaft 16 coupleable to the motor is journalled on ball or rollerbearings 17 and extends between the side plates. The shaft supports anddrives a pair of discs 18 and a central cam 19. Each disc is providedwith a'projecting peg 20 arranged to engage the rack grooves 11 on eachside of the block 1 such that rotation of the disc by the drive motor,acting through shaft 16, moves the block relative to the slides.

A union or sealing member 21 is interposed between the top of the blockand the cam 19 the said member having the form of a flat disc pivotallysupported on a stirrup shaped strap 22. A passage way 23 formed withinthe disc connects with inlet duct 4 and communicates with a centralopening 24 in the lower face of the disc. An annular groove 25 andO-ring 26 contained therein provide a high pressure seal between theupper surface of the block 1 and the disc. The upper face of the disc iscentrally recessed to accept a slightly resilient circular pad 27. Pad27 may be formed of nylon. The strap 22 is itself pivoted on a cross bar28 extending between the side plates, such that rotation of the cam 19pushes the disc into abutment with the upper surface of the block.

The outlet duct 5 connects with a centrally apertured bottom connectorpiece 29 located vertically below the sealing number 21. The upper face30 of the connector piece is provided with an annular groove 31containing an O-ring 32. O-ring 32 lightly contacts the under surface ofthe block 1 when the block is being moved on the guide rails.

In operation, the block having a number of sample containers located inthe appropriate apertures is moved by energising the drive motor torotate the disc 18 in a step-wise fashion. The projecting peg on eachdisc engages a groove 11 in the block and the block moves through oneincrement equal to the spacing distance between each sample container.Initial setting of the disc position ensures that each sample containeris moved into accurate register with the upper sealing member 21 and thebottom connector 29. The cam 19 is arranged such that pressure isapplied to the upper sealing member 21 via the resilient pad 27 when thesample container is correctly positioned in relation to the inlet andoutlet and the sealing member is then pressed downwards on to the block.Due to the resilience of the guide rail mountings, the block and guiderail mountings deflect slightly and apply a pressure to the connectorblock. Since both the O-rings 26 and 32 are partially deformed by thepressure applied by the cam the sample container is effectivelyconnected in a leak tight manner with the ducts leading from an eluentsupply line or pump and the analytical column.

The samples are preferably absorbed on an ion exchange media held in thesample containers and regeneration and re-equilibration are carried outat the end of each analytical cycle before the next sample is brought online. The apparatus operates automatically being controlled by a simpleprogram.

The motor drive may be programmed or controlled in any conventionalmanner which permits a time-controlled stepwise operation and in apreferred arrangement the flow of eluent through the sample iscontrolled by a selector valve also operated in accordance with thedesired program. For example, the cam 19 can be arranged to open andclose a valve (not shown) in the eluent supply line.

It will be appreciated that the invention is in no way limited to theembodiment shown. For example, other forms of transfer member can beenvisaged, i.e. a turntable, driving or roller chain or belt may beused, the stepwise motion being suitably arranged in association withthe desired sample spacing.

We claim:

1. Apparatus for automatically loading samples for analysis on to achromatography column comprising a transfer member movable along a path,a plurality of sample locating chambers located in a spaced relationshipon said transfer member and extending through said member, a fluid inletduct and a fluid outlet duct, said fluid outlet duct leading to saidcolumn, said ducts being located, relative to said transfer member to beconnected with successive chambers, means for sealing both ducts toopposite sides of a fluid passageway through a given chamber with whichthe ducts are connected, such that fluid can flow from said inlet ductthrough the given chamber and through the outlet duct, and means forstepwise moving the transfer member such that each chamber is, in turn,simultaneously registerable with said inlet and outlet ducts.

2. Apparatus for automatically loading samples for analysis on to achromatography column comprising a transfer member movable along a path,a plurality of apertures in a spaced relationship in said member andextending through said member, sample support means for locating andsupporting sample in each aperture, means for stepwise moving the membersuch that each sample support means in each aperture is held inexclusive register with fluid inlet and outlet ducts and fluid sealingmeans between the member and each of the said ducts for sealing theducts to opposite sides of a fluid passage way through the samplesupport means in exclusive register with h duc 41911 hat fluids flowfrom said inlet duct through the sample support means and through theoutlet duct.

3. Apparatus according to claim 2, wherein the transfer member isresiliently supported and cam means are provided to depress the transfermember on said supports, a sealing member incorporating one of saidfluid ducts and a deformable fluid sealing means interposed between thecam and one face of the transfer member and second deformable fluidsealing means interposed between the other fluid duct and a face of thetransfer member such that movement of the cam clamps the transfer memberbetween the fluid ducts and deforms the sealing means.

4. Apparatus according to claim 2 wherein the transfer member comprisesa turntable having the said chambers arranged in spaced relationshiparound a circle.

5. Apparatus according to claim 2 wherein the transfer member is a belthaving said chambers in spaced relationship along said belt.

6. An apparatus according to claim 2 wherein a sample support materialis inserted in at least one of said sample support means.

7. An apparatus according to claim 6 wherein said sample supportmaterial is an absorbent material.

8. An apparatus according to claim 7 wherein said absorbent material isan ion exchange medium.

9. An apparatus according to claim 7 wherein said absorbent material isa resin.

10. Apparatus for automatically loading samples for analysis on to achromatography column comprising a resiliently supported transfermember, a plurality of sample locating chambers located in spacedrelationship in said transfer member, means for stepwise moving themember such that each chamber is held in exclusive register with fluidinlet and outlet ducts, fluid sealing means between the transfer memberand each of said ducts, and cam means to depress the said transfermember on said supports and clamp the transfer member between the fluidducts.

11. Apparatus according to claim 10 wherein the transfer membercomprises a rectangular block having a plurality of apertures arrangedin a spaced linear relationship and the sample locating means include acontainer positionable in each aperture.

12. Apparatus according to claim 11 wherein the block is slidablymounted on guide rails and each upper longitudinal edge of the block isprovided with a series of vertical grooves forming a toothed rack andthe drive means for the block include a pair of spaced discs, each dischaving a projecting peg engageable with said rack.

13. Apparatus according to claim 12 wherein the cam and said discs aremounted on a common drive shaft.

14. Apparatus for automatically loading samples for analysis onto achromatography column comprising a transfer member having a plurality ofsample locating chambers located in spaced relationship in said transfermember, each chamber being in the form of a bore extending through thetransfer member, a fluid flow assembly including a fluid inlet duct anda fluid outlet duct, the two said ducts being located to besimultaneously registerable with a given chamber sealing the two ductsto' the chamber such that fluid can flow from said inlet duct throughthe chamber to said outlet duct, said transfer member and said fluidflow assembly being relatively movable such that the two said ducts canregister, in turn, with successive chambers of said transfer member.

15. An apparatus according to claim 14 including a force exerting meansfor causing at least one of said fluid ducts to be located against andaway from said transfer member, such that the said relative movementbetween the transfer member and the fluid flow assembly takes place whenthe said at least one fluid duct is in its position away from thetransfer member, and such that fluid flow through that chamber inregister with the ducts takes place when the said one duct is in itsposition against the transfer member.

16. A apparatus according to claim 15 wherein said force exerting meanscomprises a resilient transfer member supporting structure permittinglimited resilient movement of said transfer member towards and away fromsaid at least one fluid duct, and including sealing means between eachof said fluid ducts and the chamber in register therewith, and apressure exerting member for forcing into fluid tight engagement witheach other the ducts and the chamber in register there with, to form aclosed fluid flow path between the ducts through the chamber.

17. An apparatus according to claim 15 including drive means for movingthe said transfer member while the said fluid flow assembly is heldgenerally stationary, such that successive chambers are moved intoregistry with said fluid flow assembly.

18. An apparatus according to claim 17 wherein said drive means includesa member which, while moving continuously, moves the said transfermember in steps.

19. An apparatus according to claim 18 wherein each of said ductsincludes sealing means for sealing the ducts to the chambers of thetransfer member in register with the said ducts.

20. An apparatus as claimed in claim 19 wherein the transfer member isresiliently supported for movement towards and away from said at leastone fluid flow duct, and including a force exerting means operable intimed relationship with said drive means for forcing into fluid tightengagement with each other the ducts and the chamber in refister withthe ducts.

References Cited UNITED STATES PATENTS 3,240,068 3/ 1966 Horeth et al73--421.5 3,038,340 6/1962 Isreeli.

3,162,050 12/1964 MacDonald et a1.

3,239,312 3/1964 Bell et al.

LOUIS R. PRINCE, Primary Examiner HARRY C. POST, Assistant Examiner US.Cl. X.R.

